Pharmaceutical Targeting of Eosinophils by CCR-3 Mediated Internalization

Pharmaceutical Targeting of Eosinophils by CCR-3 Medicated Internalization

(CHMC Ref. Id: 1999-0210)

Overview: 

Eosinophils normally appear in peripheral blood at a concentration of ~1-3% of total leukocytes and their presence in tissue is primarily restricted to the mucosa. However, in various disease states, such as eosinophilic esophagitis (EoE), eosinophils appear in increased numbers in peripheral blood and/or tissues, a condition known as eosinophilia. Tissue accumulation of eosinophils may cause potent pro-inflammatory effects. Numerous pharmacologic agents such as glucocorticoids, have been used to treat a variety of eosinophil-related diseases; however, none are specifically targeted to eosinophils.

Researchers at Cincinnati Children's have discovered methods that specifically target eosinophil function and trafficking by using intracellular targeting via the CC chemokine receptor-3 (CCR3), a major chemokine receptor on eosinophils. The method involves providing a ligand for CCR3 that forms a ligand-receptor complex, which is internalized into the cell, and then can alter the cells function. The ligand may also have a compound attached to it, such as a toxin, drug, enzyme, radiomolecule, which may be activated intracellularly. Such methods can be designed to alter a specific cellular function or kill the cell as appropriate.

Applications: 

• Therapeutic for eosinophilic-related diseases and other allergic and inflammatory disorders
• Methods may also be applicable to diseases or conditions involving basophils, lymphocytes, and/or microglial cells

Advantages:

• Direct therapeutic for eosinophil-related diseases and other inflammatory disorders
• Therapeutic specifically targeted to eosinophils (or basophils, lymphocytes, and/or microglial cells)
• Increased therapy effectiveness

Patent Information:

• Patent Issued (US 6,358,697)

Cincinnati Children's Lead Inventor:

Marc Rothenberg, M.D., PhD